Chronic Hepatitis B
Conditions
Keywords
tenofovir, adefovir, hepatitis B virus, HBeAg Negative
Brief summary
This primary objectives of this study are to compare the efficacy, safety, and tolerability of tenofovir disoproxil fumarate (TDF) versus adefovir dipivoxil (ADV) for the treatment of pre-core mutant chronic hepatitis B. Participants will receive TDF or ADV for 48 weeks (double-blind). After 48 weeks, eligible participants switched to open-label TDF for up to 480 weeks.
Interventions
DRUGTDF
300 mg tablet administered orally once daily
DRUGADV
10 mg tablet administered orally once daily
DRUGTDF placebo
Tablet administered orally once daily
DRUGADV placebo
Tablet administered orally once daily
DRUGFTC/TDF
200/300 mg fixed-dose combination (FDC) tablet administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B s-antigen (HBsAg) for at least 6 months. * 18 through 69 years of age, inclusive. * Active hepatitis B e-antigen (HBeAg) negative chronic HBV infection, with all of the following: * HBeAg negative and HBeAb positive at screening * Alanine aminotransferase (ALT) levels \> the upper limit of the normal range (ULN) and ≤ 10 x ULN * Serum HBV DNA \> 100,000 copies/mL at screening * Creatinine clearance ≥ 70 mL/min * Hemoglobin ≥ 8 g/dL * Neutrophils ≥ 1,000 /mL * Knodell necroinflammatory score ≥ 3 and a Knodell fibrosis score \< 4; however, up to 120 patients with cirrhosis, ie, a Knodell fibrosis score equal to 4, will be eligible for enrollment * Negative serum β-human chorionic gonadotropin (hCG) * Nucleotide naive, ie, no prior nucleotide (TDF or ADV) therapy for greater than 12 weeks * Nucleoside naive, ie, no prior nucleoside (any nucleoside) therapy for greater than 12 weeks. However, up to 120 patients with \> 12 weeks prior lamivudine experience will be eligible * Willing and able to provide written informed consent * Had a liver biopsy performed within 6 months of baseline and has readable biopsy slides or agrees to have a biopsy performed prior to baseline Key
Exclusion criteria
* Pregnant women, women who are breast feeding, or women who believe they may wish to become pregnant during the course of the study * Males and females of reproductive potential who are unwilling to use an effective method of contraception during the study. * Decompensated liver disease defined as conjugated bilirubin \> 1.5 x ULN, prothrombin time (PT) \> 1.5 x ULN, platelets \< 75,000/mL, serum albumin \< 3.0 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage) * Received any nucleoside, nucleotide (TDF or ADV) or interferon (pegylated or not) therapy within 6 months prior to the pre treatment biopsy * Evidence of hepatocellular carcinoma (HCC) * Coinfection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV) * Significant renal, cardiovascular, pulmonary, or neurological disease * Received solid organ or bone marrow transplantation * Is currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion * Has proximal tubulopathy Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48 | Baseline; Week 48 | Complete response was a composite endpoint defined as histological response and HBV DNA \< 400 copies/mL. Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4. A participant was a nonresponder for the primary endpoint if either biopsy (baseline or end-of-treatment) was missing or if there was not an HBV DNA value available at or beyond Week 40. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 96 | Week 96 | — |
| Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 | Weeks 144, 192, 240, 288, 336, and 384 | — |
| Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480 | Weeks 432 and 480 | — |
| Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | — |
| Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | — |
| Percentage of Participants With Histological Response at Week 48 | Baseline; Week 48 | Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4. |
| Percentage of Participants With Histological Response at Week 240 | Baseline; Week 240 | Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4. |
| Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48 | Baseline; Week 48 | The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, and ranges from 0 (best) to 14 (worst). The Ishak score measures the degree of liver fibrosis (scarring) caused by chronic necroinflammation (inflammation leading to cell death) and ranges from 0 (best) to 6 (worst). |
| Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240 | Baseline; Week 240 | The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, and ranges from 0 (best) to 14 (worst). The Ishak score measures the degree of liver fibrosis (scarring) caused by chronic necroinflammation (inflammation leading to cell death) and ranges from 0 (best) to 6 (worst). |
| Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | Baseline; Week 48 | Participants were ranked as having improvement, no change, worsening, or missing data (compared to Baseline) based on the Knodell scoring system, and results are presented as the percentage of participants in each category. The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, which ranges from 0 (best) to 14 (worst). The Knodell fibrosis domain score ranges from 0 (best) to 4 (worst). A decrease of 1 point or more indicated improvement, and an increase of 1 point or more indicated worsening. |
| Ranked Assessment of Necroinflammation and Fibrosis at Week 240 | Baseline; Week 240 | Participants were ranked as having improvement, no change, worsening, or missing data (compared to Baseline) based on the Knodell scoring system, and results are presented as the percentage of participants in each category. The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, which ranges from 0 (best) to 14 (worst). The Knodell fibrosis domain score ranges from 0 (best) to 4 (worst). A decrease of 1 point or more indicated improvement, and an increase of 1 point or more indicated worsening. |
| Percentage of Participants With ALT Normalization at Week 48 | Baseline; Week 48 | ALT normalization was defined as ALT \> upper limit of normal (ULN) at baseline and within the normal range at the end of blinded treatment. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69. |
| Percentage of Participants With ALT Normalization at Weeks 96 | Baseline; Week 96 | ALT normalization was defined as ALT \> ULN at baseline and within the normal range at Week 96. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69. |
| Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 | Baseline; Weeks 144, 192, 240, 288, 336, and 384 | ALT normalization was defined as ALT \> ULN at baseline and within the normal range at the subsequent time point. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69. |
| Percentage of Participants With ALT Normalization at Weeks 432 and 480 | Baseline; Weeks 432 and 480 | ALT normalization was defined as ALT \> ULN at baseline and within the normal range at the subsequent time point. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69. |
| Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48 | Week 48 | — |
| Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | — |
| Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) at Week 48 | Baseline; Week 48 | HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at Week 48. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at Week 48. |
| Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96 | Baseline; Week 96 | HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at Week 96. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at Week 96. |
| Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Baseline; Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at the subsequent time point. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at the subsequent time point. |
| Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) | Baseline; Week 48 | Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 48, those with viral breakthrough, and those who discontinued after Week 24 with HBV DNA ≥ 400 copies/mL. |
| Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | Baseline; Weeks 49 to 96 | Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 96 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 48 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen and had HBV DNA ≥ 400 copies/mL at the time of the addition. |
| Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | Baseline; Weeks 97 to 144 | Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 144 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 96 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 96 and had HBV DNA ≥ 400 copies/mL at the time of the addition. |
| Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | Baseline; Weeks 145 to 192 | Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 192 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 144 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 144 and had HBV DNA ≥ 400 copies/mL at the time of the addition. |
| Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | Baseline; Weeks 193 to 240 | Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 240 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 192 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 192 and had HBV DNA ≥ 400 copies/mL at the time of the addition. |
| Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | Baseline; Weeks 241 to 288 | Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 288 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 240 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 240 and had HBV DNA ≥ 400 copies/mL at the time of the addition. |
| Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | Baseline; Weeks 289 to 336 | Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 336 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 288 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 288 and had HBV DNA ≥ 400 copies/mL at the time of the addition. |
| Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | Baseline; Weeks 337 to 384 | Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 384 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 336 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 336 and had HBV DNA ≥ 400 copies/mL at the time of the addition. |
| Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | Baseline; Weeks 385 to 432 | Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 432 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 384 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 384 and had HBV DNA ≥ 400 copies/mL at the time of the addition. |
| Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | Baseline; Weeks 433 to 480 | Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 480 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 432 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 432 and had HBV DNA ≥ 400 copies/mL at the time of the addition. |
| Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | — |
Countries
Australia, Bulgaria, Canada, Czechia, France, Germany, Greece, Italy, Netherlands, New Zealand, Poland, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in North America, Europe, and Australia/New Zealand. The first participant was screened on 07 June 2005. The last study visit occurred on 19 January 2016.
Pre-assignment details
846 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| TDF-TDF TDF 300 mg plus placebo to match ADV (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added emtricitabine (FTC) to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. | 250 |
| ADV-TDF ADV 10 mg plus placebo to match TDF (double-blind period), followed by TDF 300 mg (open-label period). Participants may have added FTC to their treatment regimen (as part of FTC 200 mg/TDF 300 mg FDC tablet) in the open-label period. | 125 |
| Total | 375 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Period Through Week 48 | Lost to Follow-up | 1 | 0 |
| Double-blind Period Through Week 48 | Protocol Violation | 0 | 1 |
| Double-blind Period Through Week 48 | Randomized but Not Treated | 4 | 3 |
| Double-blind Period Through Week 48 | Safety, Tolerability, or Efficacy Reason | 5 | 2 |
| Double-blind Period Through Week 48 | Withdrew Consent | 0 | 1 |
| Open-label Period: Weeks 145 - 192 | Investigator's Discretion | 2 | 0 |
| Open-label Period: Weeks 145 - 192 | Lost to Follow-up | 3 | 1 |
| Open-label Period: Weeks 145 - 192 | Withdrew Consent | 5 | 2 |
| Open-label Period: Weeks 193 - 240 | Investigator's Discretion | 1 | 1 |
| Open-label Period: Weeks 193 - 240 | Lost to Follow-up | 0 | 1 |
| Open-label Period: Weeks 193 - 240 | Safety, Tolerability, or Efficacy Reason | 2 | 0 |
| Open-label Period: Weeks 193 - 240 | Withdrew Consent | 4 | 1 |
| Open-label Period: Weeks 241 - 288 | Investigator's Discretion | 0 | 1 |
| Open-label Period: Weeks 241 - 288 | Lost to Follow-up | 2 | 1 |
| Open-label Period: Weeks 241 - 288 | Protocol Violation | 2 | 0 |
| Open-label Period: Weeks 241 - 288 | Safety, Tolerability, or Efficacy Reason | 1 | 0 |
| Open-label Period: Weeks 241 - 288 | Withdrew Consent | 5 | 1 |
| Open-label Period: Weeks 289 - 336 | Investigator's Discretion | 7 | 4 |
| Open-label Period: Weeks 289 - 336 | Lost to Follow-up | 2 | 2 |
| Open-label Period: Weeks 289 - 336 | Withdrew Consent | 0 | 1 |
| Open-label Period: Weeks 337 - 384 | Investigator's Discretion | 1 | 1 |
| Open-label Period: Weeks 337 - 384 | Lost to Follow-up | 3 | 1 |
| Open-label Period: Weeks 337 - 384 | Study Site Discontinued | 1 | 0 |
| Open-label Period: Weeks 337 - 384 | Withdrew Consent | 2 | 1 |
| Open-label Period: Weeks 385 - 432 | Investigator's Discretion | 0 | 1 |
| Open-label Period: Weeks 385 - 432 | Safety, Tolerability, or Efficacy Reason | 0 | 1 |
| Open-label Period: Weeks 433 - 480 | Lost to Follow-up | 1 | 0 |
| Open-label Period: Weeks 433 - 480 | Safety, Tolerability, or Efficacy Reason | 1 | 1 |
| Open-label Period: Weeks 433 - 480 | Withdrew Consent | 0 | 1 |
| Open-label Period: Weeks 49 - 96 | Lost to Follow-up | 2 | 0 |
| Open-label Period: Weeks 49 - 96 | Safety, Tolerability, or Efficacy Reason | 3 | 1 |
| Open-label Period: Weeks 49 - 96 | Withdrew Consent | 5 | 1 |
| Open-label Period: Weeks 97 - 144 | Lost to Follow-up | 4 | 1 |
| Open-label Period: Weeks 97 - 144 | Safety, Tolerability, or Efficacy Reason | 1 | 0 |
| Open-label Period: Weeks 97 - 144 | Withdrew Consent | 1 | 0 |
Baseline characteristics
| Characteristic | TDF-TDF | Total | ADV-TDF |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 247 Participants | 370 Participants | 123 Participants |
| Age, Continuous | 44 years STANDARD_DEVIATION 10.6 | 44 years STANDARD_DEVIATION 10.4 | 43 years STANDARD_DEVIATION 10 |
| Baseline Alanine Aminotransferase (ALT) Above the Upper Limit of the Normal (ULN) Range No | 14 participants | 21 participants | 7 participants |
| Baseline Alanine Aminotransferase (ALT) Above the Upper Limit of the Normal (ULN) Range Yes | 236 participants | 354 participants | 118 participants |
| Baseline Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) | 6.86 log10 copies/mL STANDARD_DEVIATION 1.308 | 6.90 log10 copies/mL STANDARD_DEVIATION 1.294 | 6.98 log10 copies/mL STANDARD_DEVIATION 1.266 |
| Baseline Knodell Necroinflammatory Score | 7.8 units on a scale STANDARD_DEVIATION 2.45 | 7.8 units on a scale STANDARD_DEVIATION 2.37 | 7.8 units on a scale STANDARD_DEVIATION 2.2 |
| Gender Female | 57 Participants | 85 Participants | 28 Participants |
| Gender Male | 193 Participants | 290 Participants | 97 Participants |
| Prior Lamivudine or FTC Treatment No | 207 participants | 309 participants | 102 participants |
| Prior Lamivudine or FTC Treatment Yes | 43 participants | 66 participants | 23 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 63 participants | 93 participants | 30 participants |
| Race/Ethnicity, Customized Black or African American | 8 participants | 12 participants | 4 participants |
| Race/Ethnicity, Customized More than one race | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 7 participants | 9 participants | 2 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 11 participants | 19 participants | 8 participants |
| Race/Ethnicity, Customized White | 161 participants | 242 participants | 81 participants |
| Region of Enrollment Australia | 14 participants | 22 participants | 8 participants |
| Region of Enrollment Bulgaria | 49 participants | 72 participants | 23 participants |
| Region of Enrollment Canada | 29 participants | 47 participants | 18 participants |
| Region of Enrollment Czech Republic | 7 participants | 12 participants | 5 participants |
| Region of Enrollment France | 13 participants | 18 participants | 5 participants |
| Region of Enrollment Germany | 19 participants | 30 participants | 11 participants |
| Region of Enrollment Greece | 19 participants | 28 participants | 9 participants |
| Region of Enrollment Italy | 6 participants | 6 participants | 0 participants |
| Region of Enrollment Netherlands | 1 participants | 2 participants | 1 participants |
| Region of Enrollment New Zealand | 24 participants | 36 participants | 12 participants |
| Region of Enrollment Poland | 13 participants | 24 participants | 11 participants |
| Region of Enrollment Spain | 15 participants | 21 participants | 6 participants |
| Region of Enrollment Turkey | 11 participants | 14 participants | 3 participants |
| Region of Enrollment United Kingdom | 5 participants | 7 participants | 2 participants |
| Region of Enrollment United States | 25 participants | 36 participants | 11 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 121 / 250 | 61 / 125 | 256 / 347 |
| serious Total, serious adverse events | 12 / 250 | 7 / 125 | 90 / 347 |
Outcome results
Primary
Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48
Complete response was a composite endpoint defined as histological response and HBV DNA \< 400 copies/mL. Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4. A participant was a nonresponder for the primary endpoint if either biopsy (baseline or end-of-treatment) was missing or if there was not an HBV DNA value available at or beyond Week 40.
Time frame: Baseline; Week 48
Population: Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study medication; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48 | Yes | 70.8 percentage of participants |
| TDF-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48 | No | 29.2 percentage of participants |
| ADV-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48 | Yes | 48.8 percentage of participants |
| ADV-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48 | No | 51.2 percentage of participants |
Comparison: A two-sided 95% confidence interval (CI), stratified by baseline ALT (≤ 2 x ULN or \> 2 x ULN) was used to evaluate the difference (tenofovir DF - adefovir dipivoxil) in the proportion of complete responders between treatment groups.p-value: <0.00195% CI: [13.2, 33.8]Z-test
Secondary
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Time frame: Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TDF-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 48 | -95.0 units per liter | Standard Deviation 102.31 |
| TDF-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 96 | -93.7 units per liter | Standard Deviation 106.66 |
| TDF-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 144 | -99.1 units per liter | Standard Deviation 105.67 |
| TDF-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 192 | -99.6 units per liter | Standard Deviation 109.46 |
| TDF-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 240 | -97.7 units per liter | Standard Deviation 104.32 |
| TDF-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 288 | -98.9 units per liter | Standard Deviation 104.66 |
| TDF-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 336 | -98.9 units per liter | Standard Deviation 106.5 |
| TDF-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 384 | -96.1 units per liter | Standard Deviation 105.43 |
| TDF-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 432 | -97.0 units per liter | Standard Deviation 115.09 |
| TDF-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 480 | -94.9 units per liter | Standard Deviation 117.6 |
| ADV-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 384 | -132.6 units per liter | Standard Deviation 142.09 |
| ADV-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 48 | -124.4 units per liter | Standard Deviation 137.23 |
| ADV-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 288 | -134.7 units per liter | Standard Deviation 152.9 |
| ADV-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 96 | -138.5 units per liter | Standard Deviation 155.75 |
| ADV-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 480 | -129.2 units per liter | Standard Deviation 139.24 |
| ADV-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 144 | -140.0 units per liter | Standard Deviation 155.43 |
| ADV-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 336 | -143.1 units per liter | Standard Deviation 160.15 |
| ADV-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 192 | -140.3 units per liter | Standard Deviation 153.89 |
| ADV-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 432 | -131.9 units per liter | Standard Deviation 136.65 |
| ADV-TDF | Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 240 | -139.5 units per liter | Standard Deviation 156.9 |
Secondary
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Time frame: Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TDF-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 48 | -4.57 log10 copies/mL | Standard Deviation 1.347 |
| TDF-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 96 | -4.54 log10 copies/mL | Standard Deviation 1.4 |
| TDF-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 144 | -4.61 log10 copies/mL | Standard Deviation 1.285 |
| TDF-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 192 | -4.56 log10 copies/mL | Standard Deviation 1.371 |
| TDF-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 240 | -4.59 log10 copies/mL | Standard Deviation 1.288 |
| TDF-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 288 | -4.61 log10 copies/mL | Standard Deviation 1.31 |
| TDF-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 336 | -4.61 log10 copies/mL | Standard Deviation 1.329 |
| TDF-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 384 | -4.56 log10 copies/mL | Standard Deviation 1.333 |
| TDF-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 432 | -4.60 log10 copies/mL | Standard Deviation 1.376 |
| TDF-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 480 | -4.57 log10 copies/mL | Standard Deviation 1.329 |
| ADV-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 384 | -4.79 log10 copies/mL | Standard Deviation 1.314 |
| ADV-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 48 | -4.07 log10 copies/mL | Standard Deviation 1.331 |
| ADV-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 288 | -4.81 log10 copies/mL | Standard Deviation 1.31 |
| ADV-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 96 | -4.74 log10 copies/mL | Standard Deviation 1.26 |
| ADV-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 480 | -4.75 log10 copies/mL | Standard Deviation 1.349 |
| ADV-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 144 | -4.77 log10 copies/mL | Standard Deviation 1.285 |
| ADV-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 336 | -4.81 log10 copies/mL | Standard Deviation 1.307 |
| ADV-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 192 | -4.75 log10 copies/mL | Standard Deviation 1.271 |
| ADV-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 432 | -4.69 log10 copies/mL | Standard Deviation 1.37 |
| ADV-TDF | Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 240 | -4.77 log10 copies/mL | Standard Deviation 1.303 |
Secondary
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240
The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, and ranges from 0 (best) to 14 (worst). The Ishak score measures the degree of liver fibrosis (scarring) caused by chronic necroinflammation (inflammation leading to cell death) and ranges from 0 (best) to 6 (worst).
Time frame: Baseline; Week 240
Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TDF-TDF | Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240 | Knodell Score | -4.6 units on a scale | Standard Deviation 2.5 |
| TDF-TDF | Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240 | Ishak Score | -4.0 units on a scale | Standard Deviation 2.16 |
| ADV-TDF | Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240 | Knodell Score | -4.9 units on a scale | Standard Deviation 2.53 |
| ADV-TDF | Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240 | Ishak Score | -4.2 units on a scale | Standard Deviation 2.38 |
Secondary
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48
The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, and ranges from 0 (best) to 14 (worst). The Ishak score measures the degree of liver fibrosis (scarring) caused by chronic necroinflammation (inflammation leading to cell death) and ranges from 0 (best) to 6 (worst).
Time frame: Baseline; Week 48
Population: Participants in the Randomized and Treated Analysis Set with measurements at Baseline and Week 48 were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TDF-TDF | Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48 | Knodell Necroinflammatory Score | -3.5 units on a scale | Standard Deviation 2.5 |
| TDF-TDF | Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48 | Ishak Necroinflammatory Score | -2.6 units on a scale | Standard Deviation 1.93 |
| ADV-TDF | Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48 | Knodell Necroinflammatory Score | -3.4 units on a scale | Standard Deviation 2.36 |
| ADV-TDF | Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48 | Ishak Necroinflammatory Score | -2.6 units on a scale | Standard Deviation 1.9 |
Secondary
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Time frame: Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TDF-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 144 | -0.6 units per liter | Standard Deviation 12.91 |
| TDF-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 336 | -2.6 units per liter | Standard Deviation 15.69 |
| TDF-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 240 | -2.5 units per liter | Standard Deviation 14.64 |
| TDF-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 384 | -2.9 units per liter | Standard Deviation 14.13 |
| TDF-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 192 | 0.7 units per liter | Standard Deviation 23.07 |
| TDF-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 432 | -4.6 units per liter | Standard Deviation 15.65 |
| TDF-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 288 | -3.9 units per liter | Standard Deviation 13.35 |
| TDF-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 480 | -2.8 units per liter | Standard Deviation 15.92 |
| TDF-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 96 | 2.4 units per liter | Standard Deviation 22.01 |
| ADV-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 480 | -5.9 units per liter | Standard Deviation 24.12 |
| ADV-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 96 | -0.6 units per liter | Standard Deviation 19.87 |
| ADV-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 144 | -0.3 units per liter | Standard Deviation 22.48 |
| ADV-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 192 | -3.6 units per liter | Standard Deviation 22.77 |
| ADV-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 240 | -3.9 units per liter | Standard Deviation 20 |
| ADV-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 288 | -4.1 units per liter | Standard Deviation 22.3 |
| ADV-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 336 | -2.0 units per liter | Standard Deviation 20.61 |
| ADV-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 384 | -3.9 units per liter | Standard Deviation 21 |
| ADV-TDF | Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 432 | -8.9 units per liter | Standard Deviation 29.12 |
Secondary
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Time frame: Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TDF-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 144 | -0.03 log10 copies/mL | Standard Deviation 0.378 |
| TDF-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 336 | -0.05 log10 copies/mL | Standard Deviation 0.38 |
| TDF-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 240 | -0.04 log10 copies/mL | Standard Deviation 0.299 |
| TDF-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 384 | -0.02 log10 copies/mL | Standard Deviation 0.241 |
| TDF-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 192 | 0.01 log10 copies/mL | Standard Deviation 0.61 |
| TDF-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 432 | -0.04 log10 copies/mL | Standard Deviation 0.393 |
| TDF-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 288 | -0.04 log10 copies/mL | Standard Deviation 0.353 |
| TDF-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 480 | -0.05 log10 copies/mL | Standard Deviation 0.366 |
| TDF-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 96 | 0.02 log10 copies/mL | Standard Deviation 0.424 |
| ADV-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 480 | -0.72 log10 copies/mL | Standard Deviation 1.283 |
| ADV-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 96 | -0.60 log10 copies/mL | Standard Deviation 1.138 |
| ADV-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 144 | -0.63 log10 copies/mL | Standard Deviation 1.169 |
| ADV-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 192 | -0.61 log10 copies/mL | Standard Deviation 1.161 |
| ADV-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 240 | -0.61 log10 copies/mL | Standard Deviation 1.195 |
| ADV-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 288 | -0.64 log10 copies/mL | Standard Deviation 1.203 |
| ADV-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 336 | -0.65 log10 copies/mL | Standard Deviation 1.23 |
| ADV-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 384 | -0.66 log10 copies/mL | Standard Deviation 1.237 |
| ADV-TDF | Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 | Week 432 | -0.67 log10 copies/mL | Standard Deviation 1.378 |
Secondary
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 144 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 96 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 96 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time frame: Baseline; Weeks 97 to 144
Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 96 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 2 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 1 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | Participants evaluated | 4 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | Unable to genotype | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | Participants evaluated | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | Participants evaluated | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
Secondary
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 192 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 144 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 144 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time frame: Baseline; Weeks 145 to 192
Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 144 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | Unable to genotype | 1 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | Participants evaluated | 3 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 1 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | Participants evaluated | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) | Participants evaluated | 0 participants |
Secondary
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 240 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 192 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 192 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time frame: Baseline; Weeks 193 to 240
Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 192 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | Participants evaluated | 1 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 1 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 2 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | Participants evaluated | 2 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | Unable to genotype | 2 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | Participants evaluated | 2 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
Secondary
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 288 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 240 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 240 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time frame: Baseline; Weeks 241 to 288
Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 240 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 1 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 2 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | Participants evaluated | 3 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | Participants evaluated | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | Participants evaluated | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
Secondary
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 336 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 288 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 288 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time frame: Baseline; Weeks 289 to 336
Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 288 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | Participants evaluated | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | Participants evaluated | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | Unable to genotype | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | Participants evaluated | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
Secondary
Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 384 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 336 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 336 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time frame: Baseline; Weeks 337 to 384
Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 336 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | Participants evaluated | 1 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | Unable to genotype | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | Participants evaluated | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | Participants evaluated | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
Secondary
Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 432 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 384 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 384 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time frame: Baseline; Weeks 385 to 432
Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 384 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 2 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | Participants evaluated | 2 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | Participants evaluated | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | Participants evaluated | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
Secondary
Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 480 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 432 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen after Week 432 and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time frame: Baseline; Weeks 433 to 480
Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 432 with available data were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | Participants evaluated | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | Participants evaluated | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | Unable to genotype | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | Participants evaluated | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
Secondary
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 48, those with viral breakthrough, and those who discontinued after Week 24 with HBV DNA ≥ 400 copies/mL.
Time frame: Baseline; Week 48
Population: Participants in the Randomized and Treated Analysis Set were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) | Changes at conserved sites in HBV polymerase | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 4 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 3 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) | Unable to be genotyped | 1 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) | Participants evaluated | 8 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) | Unable to be genotyped | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) | Participants evaluated | 42 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) | Changes at conserved sites in HBV polymerase | 7 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 14 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 20 participants |
Secondary
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)
Of the total number analyzed, participants evaluated for resistance included those with HBV DNA ≥ 400 copies/mL at Week 96 on TDF monotherapy, those with viral breakthrough, those who discontinued after Week 48 with HBV DNA ≥ 400 copies/mL, and those who added emtricitabine to the open-label TDF regimen and had HBV DNA ≥ 400 copies/mL at the time of the addition.
Time frame: Baseline; Weeks 49 to 96
Population: Participants in the Randomized and Treated Analysis Set who continued on the study after Week 48 (ie, entered the open-label phase) were analyzed to determine if they qualified for protocol criteria for resistance surveillance, and those meeting the criteria were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 4 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 2 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | Participants evaluated | 6 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| TDF-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | Unable to be genotyped | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | Participants evaluated | 1 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | Unable to be genotyped | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | Unable to be genotyped | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | No genotypic changes (wild-type virus) | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | Participants evaluated | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | Changes at polymorphic sites in HBV polymerase | 0 participants |
| ADV-TDF | Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) | Changes at conserved sites within HBV polymerase | 0 participants |
Secondary
Percentage of Participants With ALT Normalization at Week 48
ALT normalization was defined as ALT \> upper limit of normal (ULN) at baseline and within the normal range at the end of blinded treatment. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.
Time frame: Baseline; Week 48
Population: Participants in the Randomized and Treated Analysis Set with ALT \> ULN at baseline were analyzed; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF-TDF | Percentage of Participants With ALT Normalization at Week 48 | 76.3 percentage of participants |
| ADV-TDF | Percentage of Participants With ALT Normalization at Week 48 | 77.1 percentage of participants |
p-value: 0.85995% CI: [-10.2, 8.5]Z-test
Secondary
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384
ALT normalization was defined as ALT \> ULN at baseline and within the normal range at the subsequent time point. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.
Time frame: Baseline; Weeks 144, 192, 240, 288, 336, and 384
Population: Participants in the Randomized and Treated Analysis Set with ALT \> ULN at baseline and available data were analyzed. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria; data for participants who added FTC to their open-label TDF regimen were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 | Week 144 | 74.3 percentage of participants |
| TDF-TDF | Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 | Week 192 | 68.2 percentage of participants |
| TDF-TDF | Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 | Week 240 | 70.3 percentage of participants |
| TDF-TDF | Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 | Week 288 | 69.9 percentage of participants |
| TDF-TDF | Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 | Week 336 | 65.9 percentage of participants |
| TDF-TDF | Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 | Week 384 | 65.3 percentage of participants |
| ADV-TDF | Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 | Week 336 | 65.4 percentage of participants |
| ADV-TDF | Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 | Week 144 | 70.0 percentage of participants |
| ADV-TDF | Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 | Week 288 | 72.9 percentage of participants |
| ADV-TDF | Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 | Week 192 | 76.4 percentage of participants |
| ADV-TDF | Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 | Week 384 | 69.2 percentage of participants |
| ADV-TDF | Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 | Week 240 | 75.7 percentage of participants |
Secondary
Percentage of Participants With ALT Normalization at Weeks 432 and 480
ALT normalization was defined as ALT \> ULN at baseline and within the normal range at the subsequent time point. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.
Time frame: Baseline; Weeks 432 and 480
Population: Participants in the Randomized and Treated Analysis Set with ALT \> ULN at baseline and with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Percentage of Participants With ALT Normalization at Weeks 432 and 480 | Week 432 | 86.5 percentage of participants |
| TDF-TDF | Percentage of Participants With ALT Normalization at Weeks 432 and 480 | Week 480 | 80.0 percentage of participants |
| ADV-TDF | Percentage of Participants With ALT Normalization at Weeks 432 and 480 | Week 432 | 87.2 percentage of participants |
| ADV-TDF | Percentage of Participants With ALT Normalization at Weeks 432 and 480 | Week 480 | 88.9 percentage of participants |
Secondary
Percentage of Participants With ALT Normalization at Weeks 96
ALT normalization was defined as ALT \> ULN at baseline and within the normal range at Week 96. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.
Time frame: Baseline; Week 96
Population: Participants in the Randomized and Treated Analysis Set with ALT \> ULN at baseline. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria; data for participants who added FTC to their open-label TDF regimen were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF-TDF | Percentage of Participants With ALT Normalization at Weeks 96 | 72.4 percentage of participants |
| ADV-TDF | Percentage of Participants With ALT Normalization at Weeks 96 | 68.5 percentage of participants |
p-value: 0.35995% CI: [-5.5, 15.3]Z-test
Secondary
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96
HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at Week 96. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at Week 96.
Time frame: Baseline; Week 96
Population: Randomized and Treated Analysis Set. Data is included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96 | HBsAg Loss | 0 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96 | Anti-HBs Seroconversion | 0 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96 | HBsAg Loss | 0 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96 | Anti-HBs Seroconversion | 0 percentage of participants |
Secondary
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480
HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at the subsequent time point. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at the subsequent time point.
Time frame: Baseline; Weeks 144, 192, 240, 288, 336, 384, 432, and 480
Population: Randomized and Treated Analysis Set. Data is included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria. Participants with missing values related to protocol criteria or who added FTC to their open-label TDF regimen were considered to have failed to reach the endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 144 | 0 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 144 | 0 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 192 | 0 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 192 | 0 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 240 | 0 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 240 | 0 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 288 | 0 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 288 | 0 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 336 | 0 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 336 | 0 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 384 | 0.8 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 384 | 0.4 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 432 | 1.2 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 432 | 0.4 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 480 | 1.2 percentage of participants |
| TDF-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 480 | 0.8 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 480 | 0.8 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 144 | 0 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 336 | 0.8 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 144 | 0 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 432 | 1.6 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 192 | 0 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 336 | 0.8 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 192 | 0 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 480 | 2.4 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 240 | 0.8 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 384 | 0.8 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 240 | 0 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 432 | 0.8 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | HBsAg Loss - Week 288 | 0.8 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 384 | 0.8 percentage of participants |
| ADV-TDF | Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 | Anti-HBs Seroconversion - Week 288 | 0.8 percentage of participants |
Secondary
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48
Time frame: Week 48
Population: Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48 | 93.2 percentage of participants |
| ADV-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48 | 63.2 percentage of participants |
p-value: <0.00195% CI: [21.3, 39.2]Z-test
Secondary
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384
Time frame: Weeks 144, 192, 240, 288, 336, and 384
Population: Randomized and Treated Analysis Set. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria. Participants with missing values related to protocol criteria or who added FTC to their open-label TDF regimen were considered to have failed to reach the endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 | Week 144 | 86.7 percentage of participants |
| TDF-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 | Week 192 | 84.0 percentage of participants |
| TDF-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 | Week 240 | 82.8 percentage of participants |
| TDF-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 | Week 288 | 80.5 percentage of participants |
| TDF-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 | Week 336 | 77.0 percentage of participants |
| TDF-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 | Week 384 | 74.3 percentage of participants |
| ADV-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 | Week 336 | 78.0 percentage of participants |
| ADV-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 | Week 144 | 88.4 percentage of participants |
| ADV-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 | Week 288 | 82.9 percentage of participants |
| ADV-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 | Week 192 | 86.8 percentage of participants |
| ADV-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 | Week 384 | 76.3 percentage of participants |
| ADV-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 | Week 240 | 83.9 percentage of participants |
Secondary
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480
Time frame: Weeks 432 and 480
Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added emtricitabine to their open-label TDF regimen were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480 | Week 432 | 97.6 percentage of participants |
| TDF-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480 | Week 480 | 100.0 percentage of participants |
| ADV-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480 | Week 432 | 97.7 percentage of participants |
| ADV-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480 | Week 480 | 100.0 percentage of participants |
Secondary
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 96
Time frame: Week 96
Population: Participants in the Randomized and Treated Analysis Set with available data were analyzed. Data included for participants who had discontinued unless the reason for discontinuation was unrelated to protocol criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDF-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 96 | 90.6 percentage of participants |
| ADV-TDF | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 96 | 89.3 percentage of participants |
p-value: 0.67295% CI: [-5.2, 8]Z-test
Secondary
Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) at Week 48
HBsAg loss was defined as HBsAg positive at baseline and HBsAg negative at Week 48. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at Week 48.
Time frame: Baseline; Week 48
Population: Participants in the Randomized and Treated Analysis Set were analyzed. The missing = failure approach was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) at Week 48 | HBsAg Loss | 0 percentage of participants |
| TDF-TDF | Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) at Week 48 | Seroconversion to anti-HBs | 0 percentage of participants |
| ADV-TDF | Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) at Week 48 | HBsAg Loss | 0 percentage of participants |
| ADV-TDF | Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) at Week 48 | Seroconversion to anti-HBs | 0 percentage of participants |
Secondary
Percentage of Participants With Histological Response at Week 240
Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4.
Time frame: Baseline; Week 240
Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Percentage of Participants With Histological Response at Week 240 | Yes | 87.3 percentage of participants |
| TDF-TDF | Percentage of Participants With Histological Response at Week 240 | No | 12.7 percentage of participants |
| ADV-TDF | Percentage of Participants With Histological Response at Week 240 | Yes | 85.1 percentage of participants |
| ADV-TDF | Percentage of Participants With Histological Response at Week 240 | No | 14.9 percentage of participants |
Secondary
Percentage of Participants With Histological Response at Week 48
Histological response was based on the Knodell numerical scoring of liver biopsy specimens and defined as at least a 2-point reduction in Knodell necroinflammatory score without worsening in Knodell fibrosis score. The Knodell necroinflammatory score is the combined necrosis and inflammation domain scores and ranges from 0 to 14; the Knodell fibrosis domain score ranges from 0 to 4.
Time frame: Baseline; Week 48
Population: Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Percentage of Participants With Histological Response at Week 48 | Yes | 72.4 percentage of participants |
| TDF-TDF | Percentage of Participants With Histological Response at Week 48 | No | 27.6 percentage of participants |
| ADV-TDF | Percentage of Participants With Histological Response at Week 48 | Yes | 68.8 percentage of participants |
| ADV-TDF | Percentage of Participants With Histological Response at Week 48 | No | 31.2 percentage of participants |
p-value: 0.29395% CI: [-4.5, 14.9]Z-test
Secondary
Ranked Assessment of Necroinflammation and Fibrosis at Week 240
Participants were ranked as having improvement, no change, worsening, or missing data (compared to Baseline) based on the Knodell scoring system, and results are presented as the percentage of participants in each category. The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, which ranges from 0 (best) to 14 (worst). The Knodell fibrosis domain score ranges from 0 (best) to 4 (worst). A decrease of 1 point or more indicated improvement, and an increase of 1 point or more indicated worsening.
Time frame: Baseline; Week 240
Population: Participants in the Randomized and Treated Analysis Set with observed data were analyzed; the missing-equals-excluded approach was used where participants with missing data were excluded from the analysis. Data for participants who added FTC to their open-label TDF regimen were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 240 | Improvement - Necroinflammation | 96.7 percentage of participants |
| TDF-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 240 | No Change - Necroinflammation | 2.7 percentage of participants |
| TDF-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 240 | Worsening - Necroinflammation | 0.7 percentage of participants |
| TDF-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 240 | Improvement - Fibrosis | 62.0 percentage of participants |
| TDF-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 240 | No Change - Fibrosis | 34.0 percentage of participants |
| TDF-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 240 | Worsening - Fibrosis | 4.0 percentage of participants |
| ADV-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 240 | No Change - Fibrosis | 33.8 percentage of participants |
| ADV-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 240 | Improvement - Necroinflammation | 94.6 percentage of participants |
| ADV-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 240 | Improvement - Fibrosis | 59.5 percentage of participants |
| ADV-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 240 | No Change - Necroinflammation | 1.4 percentage of participants |
| ADV-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 240 | Worsening - Fibrosis | 6.8 percentage of participants |
| ADV-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 240 | Worsening - Necroinflammation | 4.1 percentage of participants |
Secondary
Ranked Assessment of Necroinflammation and Fibrosis at Week 48
Participants were ranked as having improvement, no change, worsening, or missing data (compared to Baseline) based on the Knodell scoring system, and results are presented as the percentage of participants in each category. The Knodell necroinflammatory score is the combined score for necrosis and inflammation domains of the Knodell scoring system, which ranges from 0 (best) to 14 (worst). The Knodell fibrosis domain score ranges from 0 (best) to 4 (worst). A decrease of 1 point or more indicated improvement, and an increase of 1 point or more indicated worsening.
Time frame: Baseline; Week 48
Population: Randomized and Treated Analysis Set; the missing-equals-failure approach was used where participants with missing data were considered to have failed to reach the endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TDF-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | Improvement - Necroinflammation | 82.0 percentage of participants |
| TDF-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | No Change - Necroinflammation | 6.8 percentage of participants |
| TDF-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | Worsening - Necroinflammation | 4.8 percentage of participants |
| TDF-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | Missing Data - Necroinflammation | 6.4 percentage of participants |
| TDF-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | Improvement - Fibrosis | 22.0 percentage of participants |
| TDF-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | No Change - Fibrosis | 63.2 percentage of participants |
| TDF-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | Worsening - Fibrosis | 8.4 percentage of participants |
| TDF-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | Missing Data - Fibrosis | 6.4 percentage of participants |
| ADV-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | Missing Data - Fibrosis | 9.6 percentage of participants |
| ADV-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | Improvement - Necroinflammation | 81.6 percentage of participants |
| ADV-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | Improvement - Fibrosis | 25.6 percentage of participants |
| ADV-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | No Change - Necroinflammation | 8.0 percentage of participants |
| ADV-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | Worsening - Fibrosis | 10.4 percentage of participants |
| ADV-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | Worsening - Necroinflammation | 0.8 percentage of participants |
| ADV-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | No Change - Fibrosis | 54.4 percentage of participants |
| ADV-TDF | Ranked Assessment of Necroinflammation and Fibrosis at Week 48 | Missing Data - Necroinflammation | 9.6 percentage of participants |